Wayrilz Approved for Persistent or Chronic Immune Thrombocytopenia

The Food and Drug Administration (FDA) has approved Wayrilz^™ (rilzabrutinib) for adults with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. 

Rilzabrutinib is a small-molecule, reversible, Bruton tyrosine kinase inhibitor. In ITP, rilzabrutinib modulates immune-mediated processes by blocking B cell activation, reducing autoantibody signaling, and decreasing autoantibody production. 

The approval was based on the randomized, double-blind, parallel-group, phase 3 LUNA 3 trial (ClinicalTrials.gov Identifier: NCT04562766), which evaluated the safety and efficacy of rilzabrutinib in adults with primary persistent or chronic ITP. Enrolled patients had an unsustained response to either intravenous immunoglobulin or corticosteroids or had a documented intolerance or insufficient response to any ITP standard of care therapy. 

Patients initially received 12 weeks of treatment during a double-blind treatment period; those who achieved platelet count response were eligible to continue treatment for the full 24 weeks. An open-label period followed the end of the full 24 week blinded treatment period.

Study participants were randomly assigned 2:1 to receive rilzabrutinib 400mg (n=133) or placebo (n=69) twice daily. Concomitant ITP medications were allowed at stable doses at least 2 weeks before the start of the study and throughout the double-blind period.

At 12 weeks, 64% (n=85) of patients in the rilzabrutinib arm and 32% (n=22) of patients in the placebo arm had achieved platelet count response and were eligible to continue the full 24-week double-blind period.

The primary endpoint was durable platelet response, defined as a weekly platelet count of greater than or equal to 50 x10⁹ /L for at least two-thirds of at least 8 non-missing weekly scheduled platelet measurements during the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy, given that at least 2 non-missing platelet measurements were greater than or equal to 50 x10⁹ /L during the last 6 weeks of the blinded period. 

Findings showed 23% (95% CI, 16.12-30.49) of patients treated with rilzabrutinib achieved durable platelet response compared with none receiving placebo (risk difference, 23.1 [95% CI, 15.95-30.31]; P <.0001). 

Results also showed a longer duration of platelet response with rilzabrutinib vs placebo.

• Greater than or equal to 50 x10⁹ /L or between 30 x10⁹ /L and less than 50 x10⁹ /L and doubled from baseline: least square (LS) mean of 7.18 weeks vs 0.72 weeks (difference, 6.46 [95% CI, 4.92-7.99]; P <.0001);
• Greater than or equal to 30 x10⁹/L and doubled from baseline: LS mean of 6.95 weeks vs 0.64 weeks (difference, 6.31 [95% CI, 4.79-7.83]; P <.0001).

Additionally, rilzabrutinib was associated with a faster time to first platelet response compared with placebo (36 days vs not reached with placebo; hazard ratio, 3.10 [95% CI, 1.95-4.93]; P <.0001). In the placebo group, 58% of patients required rescue medication vs 33% of the rilzabrutinib group; median time to first use of rescue therapy was 56 days and not reached, respectively. 

Notably, during the open-label period, 10% (7/73) patients who were treated with rilzabrutinib during the double-blind period achieved a durable response for the first time. 

The most common adverse reactions reported with rilzabrutinib were diarrhea, nausea, headache, abdominal pain, and COVID-19. The prescribing information also includes warnings regarding the risks of serious infections, hepatotoxicity and embryofetal toxicity. 

Wayrilz is supplied as a 400mg tablet. The recommended dosage is 400mg twice daily, with or without food. 

This article originally appeared on MPR